Assessment of the Safety and Effect of SAR425899 Versus Placebo for the Treatment of Non-alcoholic Fatty Liver Disease

NCT03437720 | Withdrawn Phase 2 FDA Drug

• 3 other identifiers: ACT150672017-002371-26U1111-1191-5486
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary Objective: \- To evaluate the dose response relationship of SAR425899 compared to placebo on resolution of non-alcoholic steatohepatitis (NASH) with no worsening of fibrosis in diabetic and non-diabetic patients with histopathologically-confirmed NASH. Secondary Objectives:

• To assess the effect of SAR425899 on overall non-alcoholic fatty liver disease (NAFLD) activity score (NAS), individual components of NAS (steatosis, hepatocyte ballooning, and lobular inflammation), and fibrosis score.
• To assess to the effect of SAR425899 on MRI-PDFF (Magnetic Resonance Imaging-determined Proton Density Fat Fraction) derived parameters (total liver fat, liver volume, and fractional liver fat content).
• To assess the effect of SAR425889 on body weight and waist/hip circumference ratio.
• To assess SAR425899 pharmacokinetics.
• To assess safety and tolerability of SAR425899.

Conditions

Non-alcoholic Steatohepatitis; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Resolution of Non-alcoholic steatohepatitis (NASH)

  Percentage of participants with absence of hepatocyte ballooning (NAFLD - non-alcoholic fatty liver disease - activity score, NAS = 0) without worsening of fibrosis score at week 52. -

  Week 52

Secondary Outcomes (16)

• No hepatocyte ballooning, lobular inflammation score 0 or 1, without worsening of fibrosis

  Week 52

• Change in overall NAFLD activity score (NAS)

  Baseline to week 52

• Change in NAS individual components

  Baseline to week 52

• Change in NAS individual components

  Baseline to week 52

• Change in NAS individual components

  Baseline to week 52

Study Arms (4)

SAR425899 (Low Dose)

EXPERIMENTAL

Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned.

Drug: SAR425899

SAR425899 (High Dose)

EXPERIMENTAL

Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned.

Drug: SAR425899

Placebo (Low Dose)

PLACEBO COMPARATOR

Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned.

Drug: Placebo

Placebo (High Dose)

PLACEBO COMPARATOR

Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned.

Drug: Placebo

Interventions

SAR425899 DRUG

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection

SAR425899 (High Dose); SAR425899 (Low Dose)

Placebo DRUG

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection

Placebo (High Dose); Placebo (Low Dose)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-diabetic or type 2 diabetes mellitus with confirmed non-alcoholic steatohepatitis.
• Non-alcoholic fatty liver disease (NAFLD) activity score (NAS) \>=4 with each of its components \>=1.
• Patients without Type 2 diabetes determined by HbA1c (glycated hemoglobin) \<6.5% and Fasting Plasma Glucose (FPG) \<7.0 mmol/L (\<126 mg/dL).
• Stable glycemic control (HbA1c \<9.0%) and metabolic disorders managed with diet/exercise and/or stable dose metformin and/or sulphonylureas for at least 3 months prior to screening (type 2 diabetes patients).
• Signed written informed consent form.

You may not qualify if:

• Diagnosis of type 1 diabetes mellitus.
• Previous insulin use or use of insulin within the last 6 months, except for episode(s) of short-term treatment (\<15 consecutive days) due to intercurrent illness.
• Body Mass Index (BMI) \<25 kg/m2 or \>45.0 kg/m2.
• Current participation in organized diet/weight reduction program or clinical trial of weight control (within the last 3 months prior to screening), or weight loss attempt, plans for major changes in physical activities or significant change in body weight in the 2 months prior to screening (significant change in body weight is defined as \>=5% self-reported change within 6 months prior to randomization if a pre-existing liver biopsy sample was collected prior to screening period.
• Current treatment with glucose-lowering agent(s) other than metformin or sulphonylureas, weight loss drugs including orlistat, systemic steroids, methotrexate, amiodarone, or Vitamin E.
• Alcoholism (past or present) and/or average alcohol consumption per week \>21 units (210 g) for males, \>14 units (140 g) for females within the last 5 years.
• Poorly controlled hypertension (resting systolic blood pressure (SBP) \>160 mm Hg and/or resting diastolic blood pressure (DBP) \>95 mm Hg) at screening.
• Some liver diseases, pancreatic disease, liver transplantation and types of cancer.
• Pregnant or breast-feeding women.
• Women of childbearing potential (WOCBP) not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy.
• Patients with coronary, carotid, or peripheral artery revascularization procedures planned during the screening or treatment phases of the protocol.
• Patients with unstable heart conditions.
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2

Interventions

SAR425899

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2018
• First Posted: February 19, 2018
• Study Start: May 23, 2019
• Primary Completion: August 25, 2021
• Study Completion: August 25, 2021
• Last Updated: April 13, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share